Acetobromo-α-D-glucuronic acid methyl ester CAS 21085-72-3

1. Synthesis of D-glucuronic acid methyl ester. It can be represented by the following reaction formula:
   The specific preparation steps are as follows: D-glucurolactone (1) (17.6 g, 0.1 mol) was dissolved in 200 ml of methanol, and cooled to 0 °C. NaOH (100 mg) was added and stirred for 2 hours. The reaction was concentrated to dryness to give methyl D-glucuronate (2) as a white solid (yield 20.8 g, 100% yield).
2. Synthesis of methyl 1,2,3,4-tetra-O-acetyl-D-glucuronic acid. It can be represented by the following reaction formula:
   The specific preparation steps are as follows: D-glucuronic acid methyl ester (2) (20.8g, 0.1mol) was dissolved in pyridine (45ml) and cooled to below 5°C, then acetic anhydride (54mL, 0.6mol) was added dropwise to maintain stability Not exceeding 10°C, then stirring at room temperature for 3 hours. The reaction was concentrated to dryness and dissolved in 300 mL of dichloromethane, then the organic phase was washed three times with water, dried over anhydrous sodium sulfate and filtered, the filtrate was concentrated to dryness, and 100 mL of methanol was added to precipitate a solid. The solid was filtered to give methyl 1,2,3,4-tetra-O-acetyl-D-glucuronic acid (3) (yield 24.4 g, 65% yield).
3. Synthesis of acetyl bromide-α-D-glucurone acid methyl ester. It can be represented by the following reaction formula:
   The specific preparation steps are as follows: 1,2,3,4-tetra-O-acetyl-D-glucuronic acid methyl ester (3) (15.0 g, 4 mmol) was added to an acetic acid solution of hydrogen bromide (hydrogen bromide The mass percentage of 33%) (60 mL) was kept stable at no more than 10 °C, and then the temperature was naturally raised to room temperature and stirred for 2 hours. The reaction was concentrated to dryness and dissolved with 100 mL of ethyl acetate, then the organic phase was washed three times with aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate and filtered, the filtrate was concentrated to dryness, and 50 mL of petroleum ether was added to precipitate a solid. The solid was filtered to obtain A-D-glucuronic acid methyl ester (4) (yield 14.3 g, yield 90%).

To the commercially available D-glucuronic acid-6,3-lactone compound (6) (48.6 g, 276 mmol) was added anhydrous methanol (500 mL) and metallic Na (200 mg) at 0°C. The mixture was stirred under N2 for 5 hours. The solution was treated with IR-120(Ir) resin until pH3. The solvent was removed in vacuo after filtration to provide a yellow gum. The residue was partially dissolved in Ac2O (100 mL) and a solution of HClO4 (0.1 mL) in Ac2O (1 mL) was added dropwise to the reaction mixture at a rate such that the solution did not exceed 40°C. The reaction mixture was then stirred at rt under N2 overnight. The product was then dissolved in ethyl acetate, washed with 1N HCl, H2O and brine, and the organic phase was dried over Na2SO4. The solvent was removed in vacuo to afford the per-O-acetate intermediate compound (5) (96.5 g, 93%) as a white gum with alpha/beta ratio 75:25.

To the per-O-acetate compound (5) (7.73 g, 20.54 mmol) obtained above was added dropwise 45% HBr/acetic acid (25 mL) at 0°C under N2. The round bottom flask was placed in a desiccator and stirred at 4°C for 48 hours. The mixture was diluted with ethyl acetate (100 mL) and poured onto ice (50 g). The solution was washed with saturated aq. NaHCO3 (50 mL), brine (50 mL), H2O (100 mL), the organic phase was dried over Na2SO4, filtered and the solvent removed in vacuo. The product was purified by flash chromatography (2:1 hexanes/ethyl acetate) to provide glucuronyl bromide (3) (3.50 g, 43%) as a pink gum.